Abstract Circulating entities found in blood can serve as an important source of biomarkers that can be used in a variety of clinical scenarios to assist in the proper management of different diseases. Indeed, there are examples of the use of blood-borne markers for assisting in disease management such as diabetes (blood glucose levels) and a series of proteins selected from plasma used for the diagnosis of cardiovascular diseases. Unfortunately, there are a number of diseases that do not currently use circulating markers such as the cancer-related diseases and stroke. In these two examples, imaging technologies are commonly employed for diagnosis, prognosis and patient stratification to assign proper treatment regimens to particular patients (i.e., personalized medicine). While technological strides have been made in various imaging modalities, they are still fraught with limitations for example the inability to reach a large patient population especially those in resource-limited environments (70% of all cancer-related deaths occurred in low to middle income settings), undetectable disease at low burden (i.e., early detection) and the inability for making timely clinical decisions at the point-of- care (90% of all stroke patients do not receive treatment using recombinant tissue plasminogen activator due to late diagnoses secured using CT or MRI scans). TR&D Project 1 will develop innovative and transformative platforms and the associated methodologies to select from whole blood a variety of circulating biomarkers including biological cells, circulating cell-free DNA (cfDNA) and nano-vesicles (exosomes). The exciting aspect of the technology platform is that discrete task-specific modules will be designed to target each of the aforementioned markers that can be interconnected to allow processing a single sample for all three markers. The modules possess other desirable characteristics: (1) Select rare markers from whole blood with high recovery and in a high throughput format to provide important clinical information rapidly, even at the point-of- care; (2) high purity of the selected markers to allow for securing molecular information from them; and (3) simplicity in both operation and fabrication. The modules will be able to accept whole blood directly with no pre- processing required, affinity select biological cells from the sample, isolate the plasma and then, extract the plasma markers including cfDNA and exosomes. The modules will be fabricated in plastics via micro- replication, which can produce these units in a high production mode and at low-cost making them particularly attractive for in vitro diagnostics.